Objective:Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/ myeloproliferative malignancy of early childhood, characterized by monocytosis, hepatos­plenomegaly and an aggressive clinical course.
Methods: In semi-solid culture JMML progenitor cells proliferate spontaneously into colony forming units. In order to study the mechanisms of proliferation and differentiation of JMML cells we developed a suspension culture system without additional exogenous growth factor supplement. Mononuclear cells (MNC) from peripheral blood, bone marrow or spleen of 14 patients with JMML and 24 controls were studied.
Findings:JMML cells expressed higher levels of the proliferation marker Ki67 (median 24% [7-39%] vs a median of 3.5% in controls). 90% of JMML cells were CD68-positive (vs 35% in controls) and by day 7 all JMML samples contained CD1a- positive cells. Electron microscopy demonstrated cytoplasmic vesicular structures resembling multilamellar MHC II compare­timents, which together with the expression of CD1a - support a dendritic cell (DC)-phenotype.
Conclusion:Differentiation into CD1a-positive DC seems to be a frequent phenomenon in cultured JMML MNC, which in vivo may contribute to clinical characteristics such as skin and organ infiltration.